What is the use of Eplerenone (an aldosterone antagonist)?

From the Guidelines

Eplerenone should be initiated at a dose of 25 mg daily and increased to 50 mg daily after a month, as it has been shown to reduce morbidity and mortality in patients with heart failure, as evidenced by the EMPHASIS-HF trial 1. The use of eplerenone in patients with heart failure is supported by several studies, including the RALES and EMPHASIS-HF trials, which demonstrated a significant reduction in mortality and hospitalization rates 1.

• The EMPHASIS-HF trial showed that eplerenone reduced the risk of cardiovascular death or heart failure hospitalization by 37% 1.
• The typical starting dose of eplerenone is 25 mg once daily, which may be increased to 50 mg daily after four weeks based on patient response and potassium levels 1.
• Eplerenone works by blocking aldosterone receptors in the kidneys, preventing sodium reabsorption and potassium excretion, which helps reduce blood pressure and fluid retention.
• Common side effects of eplerenone include elevated potassium levels (hyperkalemia), dizziness, and fatigue, and regular monitoring of potassium levels and kidney function is essential during treatment 1.
• Eplerenone should be taken at the same time each day with or without food, and patients should maintain consistent potassium intake while using this medication.
• It's contraindicated in patients with severe kidney impairment, high potassium levels, or those taking strong CYP3A4 inhibitors 1. Key considerations for the use of eplerenone include:
• Monitoring of potassium levels and renal function, particularly in patients with marginal renal function or those at risk of hyperkalemia 1.
• Avoidance of foods high in potassium and NSAIDs, which can increase the risk of hyperkalemia 1.
• Regular monitoring of patients for signs and symptoms of hyperkalemia, such as muscle weakness, fatigue, and cardiac arrhythmias 1.

From the FDA Drug Label

Eplerenone tablets are indicated to improve survival of stable patients with symptomatic heart failure with reduced ejection fraction (≤40%) (HFrEF) after an acute myocardial infarction (MI). Eplerenone tablets are indicated for the treatment of hypertension, to lower blood pressure. The recommended starting dose of eplerenone tablets is 50 mg administered once daily. The full therapeutic effect of eplerenone tablets is apparent within 4 weeks. For patients with an inadequate blood pressure response to 50 mg once daily increase the dosage of eplerenone tablets to 50 mg twice daily Higher dosages of eplerenone tablets are not recommended because they have no greater effect on blood pressure than 100 mg and are associated with an increased risk of hyperkalemia

Eplerenone is used for two main purposes:

• Improving survival in patients with heart failure after a myocardial infarction
• Treating hypertension to lower blood pressure and reduce the risk of cardiovascular events The recommended dosage for hypertension is 50 mg once daily, which can be increased to 50 mg twice daily if necessary. Higher dosages are not recommended due to the increased risk of hyperkalemia. 2 2 2

From the Research

Eplerenone Overview

• Eplerenone is an aldosterone receptor blocker used to treat hypertension and heart failure 3, 4, 5, 6, 7
• It is indicated for use as adjunctive therapy to reduce mortality for heart failure patients with New York Heart Association (NYHA) class II systolic chronic heart failure and left ventricular systolic dysfunction 3

Clinical Use

• Eplerenone is used to treat mild and moderate essential hypertension for patients who cannot be treated adequately with other agents 3
• It has been shown to reduce morbidity and mortality in individuals with left ventricular dysfunction post myocardial infarction 6
• Eplerenone has demonstrated some renoprotective effects in diabetic patients with hypertension 7

Efficacy and Safety

• Meta-analysis of studies showed a reduction in systolic blood pressure of 9.21 mmHg and a reduction of diastolic pressure of 4.18 mmHg with eplerenone treatment 3
• The most common side effect is hyperkalemia, necessitating close monitoring in individuals with diabetes and proteinuria, heart failure, or those taking moderate CYP450 3A4 inhibitors 6
• Eplerenone is generally well tolerated, although hyperkalemia with this agent is of some concern 7

Comparison to Other Treatments

• Eplerenone has been compared to spironolactone, another mineralocorticoid receptor antagonist, and has been shown to have similar antihypertensive efficacy but with fewer hormonal side effects 5, 7
• The exact place of eplerenone in therapy will be determined by its cost and whether future studies demonstrate a clinical benefit over spironolactone or other currently available treatments 7